ArticleProceedings of the National Academy of Sciences of the United States of America2002
Excision of misincorporated ribonucleotides in DNA by RNase H (type 2) and FEN-1 in cell-free extracts.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 183 citations in OpenAlex.
- Ribonucleotide errors, RNase HII, and ribonucleotide excision repair.Critical reviews in biochemistry and molecular biology · 2026Review
- Single-molecule tracking of RNA-DNA hybrid removal enzymes important for lagging-strand replication.Biophysical journal · 2026Article
- PARP1 regulates the genomic ribonucleotide processing activity of TOP1 to prevent the formation of toxic TOP1-DNA adducts and the associated mutations.bioRxiv : the preprint server for biology · 2026Article
- Bacillus subtilis RNase HII Is Inefficient at Processing Guanosine Monophosphate and Damaged Ribonucleotides.Molecular microbiology · 2026Article
- Single-molecule tracking of RNA-DNA hybrid removal enzymes important for lagging-strand replication.bioRxiv : the preprint server for biology · 2025Article
- Deciphering the Role of DNA Polymerase Eta on the Incorporation and Bypass of Inosine and Cell Cycle Arrest.International journal of molecular sciences · 2025Article
- Nonhomologous end-joining uses distinct mechanisms to repair each strand of a double strand break.Nature communications · 2025Article
- Article
- The low endoribonuclease activity and lack of rNMP preference of human mitochondrial topoisomerase 1 protect against ribonucleotide-dependent deletions.Nucleic acids research · 2025Article
- Molecular basis for RNA discrimination by human DNA ligase 1.Nucleic acids research · 2025Article
- Investigating the origins of the mutational signatures in cancer.Nucleic acids research · 2025Review
- Processing of matched and mismatched rNMPs in DNA by archaeal ribonucleotide excision repair.iScience · 2023Article
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- Article
- Ribonucleotide Incorporation by Eukaryotic B-Family Replicases and Its Implications for Genome Stability.Annual review of biochemistry · 2022Review
- Reconsidering the Chemical Nature of Strand Breaks Derived from Abasic Sites in Cellular DNA: Evidence for 3'-Glutathionylation.Journal of the American Chemical Society · 2022Article
- Mitochondrial DNA Instability in Mammalian Cells.Antioxidants & redox signaling · 2022Review
- The catalytic mechanism, metal dependence, substrate specificity, and biodiversity of ribonuclease H.Frontiers in microbiology · 2022Review
- Manganese Is a Strong Specific Activator of the RNA Synthetic Activity of Human Polη.International journal of molecular sciences · 2021Article
- Review
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Misincorporated ribonucleotides in DNA will cause DNA backbone distortion and may be targeted by DNA repair enzymes. Using double-stranded oligonucleotide probes containing a single ribose, we demonstrate a robust activity in human, yeast, and Escherichia coli cell-free extracts that nicks 5' of the ribose. The human and yeast extracts also make a subsequent cut 3' of the ribonucleotide releasing a ribonucleotide monophosphate. The resulting 1-nt gap is an ideal substrate for polymerase and ligase to complete a proposed repair sequence that effectively replaces the ribose with deoxyribose. Screening of yeast deletion mutant cells reveals that the initial nick is made by RNase H(35), a RNase H type 2 enzyme, and the second cut is made by Rad27p, the yeast homologue of human FEN-1 protein. RNase H type 2 enzymes are present in all kingdoms of life and are evolutionarily well conserved. We knocked out the corresponding rnhb gene in E. coli and show that extracts from this strain lack the nicking activity. Conversely, a highly purified archaeal RNase HII type 2 protein has a pronounced activity. To study substrate specificity, extracts were made from a yeast double mutant lacking the other main RNase H enzymes [RNase H1 and RNase H(70)], while maintaining RNase H(35). It was found that a single ribose is preferred as substrate over a stretch of riboses, further strengthening a proposed role of this enzyme in the repair of misincorporated ribonucleotides rather than (or in addition to) processing RNADNA hybrid molecules.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.